Appetite suppressant compositions and methods thereof

ABSTRACT

An appetite suppressant composition may comprise at least one anorectic active ingredient; at least one of a nutritive substance, a cofactor; and optionally, an excipient. The anorectic active ingredient may comprise any one of phentermine, phendimetrazine, diethylpropion, naltrexone, and bupropion. The nutritive substance may comprise a protein source such as bovine collagen. The cofactor may comprise a chromium or selenium salt. In various embodiments, the compositions herein are provided in an oral capsule dosage form for GI-tract administration of the AAI. A method of suppressing appetite in individuals in need thereof are described.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of, claims priority to and thebenefit of, U.S. application Ser. No. 16/808,084, filed Mar. 3, 2020 andentitled “Appetite Suppressant Compositions and Methods Thereof,” thedisclosure of which is incorporated herein by reference in its entiretyfor all purposes.

FIELD

This disclosure generally relates to pharmaceutical compositions, andmore specifically, to orally administered appetite suppressantcompositions and methods thereof.

BACKGROUND

Individuals from wealthy industrialized countries are increasinglyobsessed by health and beauty. These individuals help fuel amulti-billion dollar market for OTC diet products, medically assistedweight loss such as prescription drugs and bariatric surgery, cosmeticsurgery and cosmetics and anti-aging treatments. Some individuals finddifficulty maintaining proper diet and exercise regiment, and are oftenturning to formulations and programs promoting rapid weight loss andbody sculpting.

In the United States, an alarming percentage of the population is obese,yet the requirements for gastric bypass surgery remains that one bemedically diagnosed obese. Others may find the surgery to not be worththe risk.

In view of these and other personal and physiological challenges inachieving and managing a healthy weight, new weight managementcompositions and health programs are still needed.

SUMMARY

In various embodiments, new appetite suppressant compositions aredescribed. In various embodiments, appetite suppressant compositions arecompounded in a dosage form for oral administration.

In various embodiments, new appetite suppressant compositions comprisean immediate release oral dosage form or a controlled release oraldosage form.

In various embodiments, new appetite suppressant compositions comprisean immediate release capsule oral dosage form.

In various embodiments, new appetite suppressant compositions comprise acontrolled release capsule oral dosage form.

In various embodiments, an appetite suppressant composition comprises atleast one anorectic active ingredient; at least one of a nutritivesubstance, a cofactor; and optionally, an excipient.

In various embodiments, the anorectic active ingredient is selected fromthe group consisting of diethylpropion, amphetamine, benfluorex,bupropion, butanolide, caffeine, cathine, cetilistat, clobenzorex,D-fenfluramine, racemic-fenfluramine, ephedrine, etilamfetamine,exenatide, FG-7142 (diazepine inverse agonist), higenamine, liraglutide,lorcaserin, mazindol, mefenorex, metformin, methamphetamine, naltrexone,nicotine, orlistat, phenmetrazine, phendimetrazine, phentermine,phenylpropanolamine, pramlinatide, pseudoephedrine,pyroglutamyl-histidyl-glycine, rimonabant, semaglutide, sibutramine,topiramate, yohimbine, pro-drugs thereof, pharmaceutically acceptablesalts thereof, and mixtures thereof.

In various embodiments, the nutritive substance is selected from thegroup consisting of a dried Spirulina algal species biomass powder, adried Chlorella algal species biomass powder, a hydrolyzed powderedbovine or fish collagen, a bovine or porcine gelatin powder, egg albuminpowder, calcium caseinate powder, powdered milk protein concentrate,whey protein isolate powder, yellow pea protein isolate, and mixturesthereof.

In various embodiments, the cofactor is selected from the groupconsisting of calcium acetate, calcium ascorbate, calcium citrate,calcium gluconate, calcium nicotinate, calcium picolinate, chromiumacetate, chromium ascorbate, chromium citrate, chromium gluconate,chromium nicotinate, chromium picolinate, copper acetate, copperascorbate, copper citrate, copper gluconate, copper nicotinate, copperpicolinate, magnesium acetate, magnesium ascorbate, magnesium citrate,magnesium gluconate, magnesium nicotinate, magnesium picolinate,manganese acetate, manganese ascorbate, manganese citrate, manganesegluconate, manganese nicotinate, manganese picolinate, potassiumacetate, potassium ascorbate, potassium citrate, potassium gluconate,potassium nicotinate, potassium picolinate, selenium acetate, seleniumascorbate, selenium citrate, selenium gluconate, selenium nicotinate,selenium picolinate, zinc acetate, zinc ascorbate, zinc citrate, zincgluconate, zinc nicotinate, zinc picolinate, and mixtures thereof.

In various aspects of an appetite suppressant composition, the anorecticactive ingredient comprises phendimetrazine tartrate, the nutritivesubstance comprises hydrolyzed powdered bovine or fish collagen, and thecofactor comprises calcium picolinate, chromium picolinate, copperpicolinate, magnesium picolinate, manganese picolinate, seleniumpicolinate, or zinc picolinate. A pharmaceutical dosage form for oraladministration comprises a capsule and this composition enclosedtherein.

In various aspects of an appetite suppressant composition, the anorecticactive ingredient comprises diethylpropion-HCl with 1% tartaric acid,the nutritive substance comprises hydrolyzed powdered bovine or fishcollagen, and the cofactor comprises calcium picolinate, chromiumpicolinate, copper picolinate, magnesium picolinate, manganesepicolinate, selenium picolinate, or zinc picolinate. A pharmaceuticaldosage form for oral administration comprises a capsule and thiscomposition enclosed therein.

In various embodiments, an appetite suppressant composition consistsessentially of from 12.0 wt. % to 18.0 wt. % phendimetrazine tartrate;from 80.0 wt. % to 90.0 wt. % bovine collagen; and from 0.05 wt. % to0.10 wt. % chromium picolinate. A pharmaceutical dosage form for oraladministration comprises a capsule and this composition enclosedtherein.

In various embodiments, a method of suppressing appetite in anindividual comprises orally administering to the individual in needthereof a therapeutically effective amount of an appetite suppressantcomposition consisting essentially of from 12.0 wt. % to 18.0 wt. %phendimetrazine tartrate; from 80.0 wt. % to 90.0 wt. % bovine collagen;and from 0.05 wt. % to 0.10 wt. % chromium picolinate. An appetitesuppressant dosage form consists essentially of 250 mg to 300 mg of thiscomposition as a loose powder and a dissolvable capsule encapsulatingsaid composition.

In various embodiments, the therapeutically effective amount comprisesorally administering up to 210 mg per day of the phendimetrazinetartrate.

In various embodiments, the individual in need thereof is diagnosedoverweight and obese.

In various embodiments, an appetite suppressant composition consistsessentially of from 6.0 wt. % to 12.0 wt. % diethylpropion-HCl, saiddiethylpropion-HCl including 1% tartaric acid; from 50.0 wt. % to 58.0wt. % bovine collagen; and from 0.05 wt. % to 0.10 wt. % chromiumpicolinate. A pharmaceutical dosage form for oral administrationcomprises a capsule and this composition enclosed therein.

In various embodiments, a method of suppressing appetite in anindividual comprises orally administering to the individual in needthereof a therapeutically effective amount of an appetite suppressantcomposition consisting essentially of from 6.0 wt. % to 12.0 wt. %diethylpropion-HCl, said diethylpropion-HCl including 1% tartaric acid;from 50.0 wt. % to 58.0 wt. % bovine collagen; and from 0.05 wt. % to0.10 wt. % chromium picolinate. An appetite suppressant dosage formconsists essentially of 250 mg to 300 mg of this composition as a loosepowder and a dissolvable capsule encapsulating said composition.

In various embodiments, the therapeutically effective amount comprisesorally administering up to 150 mg per day of the diethylpropion-HCl.

In various embodiments, the individual in need thereof is diagnosedoverweight and obese.

DETAILED DESCRIPTION

The detailed description of exemplary embodiments refers to theaccompanying drawings, which show exemplary embodiments by way ofillustration and best mode. While these exemplary embodiments aredescribed in enough detail to enable those skilled in the art topractice the invention, other embodiments may be realized, and logical,chemical, and mechanical changes may be made without departing from thespirit and scope of the inventions. Thus, the detailed description ispresented for purposes of illustration only and not of limitation. Forexample, unless otherwise noted, the steps recited in any of the methodor process descriptions may be executed in any order and are notnecessarily limited to the order presented. Furthermore, any referenceto singular includes plural embodiments, and any reference to more thanone component or step may include a singular embodiment or step. Also,any reference to attached, fixed, connected or the like may includepermanent, removable, temporary, partial, full and/or any other possibleattachment option. Additionally, any reference to without contact (orsimilar phrases) may also include reduced contact or minimal contact.

Appetite suppressant compositions comprising an appetite suppressantpharmaceutical active, (e.g., an anorectic active ingredient, or “AAI”)are described. In various embodiments, an appetite suppressantcomposition in accordance with the present disclosure comprises: atleast one AAI; and any one of or combination of nutritive substances,controlled drug release agents (“CDRAs”), cofactors, excipients, and/orfillers.

Definitions

As used herein, the terms “anorectic,” or “appetite suppressant,” or“anorectic pharmaceutical active,” or “anorectic AI” (AI=activeingredient), or most simply, the acronym “AAI,” refer to any chemicalsubstance now known or yet to be discovered that is capable ofsuppressing the feeling of hunger and/or the craving for food in anindividual, regardless if the chemical substance is currently registeredwith a regulatory agency, such as the United States Food & DrugAdministration (FDA) or not. For example, an AAI for use herein maycomprise a chemical newly synthesized in a research laboratory, or anatural product just having been isolated, and not yet presented to anyregulatory agency which might never be registered. Included in the broadclass of known AAIs are the very familiar alkaloids caffeine andnicotine. Some AAIs mentioned for use herein may have additionalpharmacological effects besides appetite suppression, e.g.,anti-obesity, or might indirectly provide appetite suppression as aconsequence or artifact of a primary pharmacological effect (e.g.,glucose production controlled by diabetes medications). Currentregulatory status, including withdrawal from registered use, is notconsidered since prior regulatory issues could have been related tophysical dosage forms or administration routes and practices that arenot within the scope of the present disclosure.

In various embodiments, AAIs that find use in the present appetitesuppressant compositions in accordance with the present disclosureinclude, but are not limited to, amfepramone (diethylpropion),amphetamine and analogs thereof, benfluorex, bupropion, butanolide,caffeine, cathine, cetilistat, clobenzorex, dexfenfluramine(D-fenfluramine), ephedrine, etilamfetamine, exenatide,racemic-fenfluramine, FG-7142, higenamine, liraglutide, lorcaserin,mazindol, mefenorex, metformin, methamphetamine and analogs thereof,naltrexone, nicotine, orlistat, phenmetrazine, phendimetrazine,phentermine, phenylpropanolamine, pramlinatide, pseudoephedrine,pyroglutamyl-histidyl-glycine, rimonabant, semaglutide, sibutramine,topiramate, yohimbine, pro-drugs thereof, pharmaceutically acceptablesalts thereof, and combinations thereof. Any of these AAIs may becommercially obtained and pharmaceutically administered as a salt, e.g.,a hydrochloride salt or a tartrate salt. For simplicity, reference ismade to the active without the —HCl or -tartrate suffix designation. Invarious embodiments, whole plant or fungal material (e.g., ephedra (MaHuang), bitter melon, maitake, purslane, tea), or any plant, root, bark,tree or flower extract, may be used as an AAI herein, recognizing thatthe appetite suppressant effect may be more of any one of a homeopathiceffect, prophylactic effect, sensory effect, placebo effect, orpsychological effect effect rather than a recognizable physiologicaleffect describable by biochemical pathways.

AAIs for use herein may comprise drugs characterizable or otherwiseknown as stimulants, antidiabetic agents, glucose regulating agents,thyroid hormones, thyroid drugs, parathyroid drugs, vitamins,antihyperlipidemic agents, cardiac drugs, respiratory drugs, nasaldecongestants, gastrointestinal drugs, amphetamines, anorexiants,antirheumatic agents, anti-gout agents, migraine drugs, sedatives,hypnotics, antianxiety drugs, anticonvulsants, antidepressants,antipsychotic agents, psychotherapeutic drugs, antimicrobials,antifungals, sulfonamides, antimalaria drugs, antituberculotic drugs,amebicides, antiviral agents, anti-infectives, leprostatics,antihelmintics, antihistamines, antimetabolites, anticholinergics,steroidal anti-inflammatories, anesthetics, antiplatelet drugs, NSAIDs,ace inhibitors, calcium channel blockers, alpha-blockers, musclerelaxers, antihypertensives, vasodilators, diuretics, antiemetics, sexhormones, pituitary hormones, analgesics, uterine hormones, and adrenalsteroid inhibitors. Such drugs might have a primary known physiologicaluse, like a stimulant, but also a secondary appetite suppressant effect.

As used herein, the term “cofactor” refers to a non-protein substancethat associates with an enzyme in order for the enzyme to function invivo. In general, enzyme cofactors include both inorganic ions, such asmetal cations, and organic molecules including a number of vitamins andnucleotides. For use herein, metal cation cofactors include, but are notlimited to, Ba²⁺, Ce³⁺, Cd²⁺, Co²⁺, Co³⁺, Cr²⁺, Cr³⁺, Cr⁶⁺, Cu¹⁺, Cu²⁺,Fe²⁺, Fe³⁺, K⁺¹, La³⁺, Mg²⁺, Mn⁺², Mn³⁺, Mo²⁺, Mo³⁺, Mo⁴⁺, Mo⁺⁵, Ni¹⁺,Ni²⁺, Se²⁺, Zn²⁺, iron-sulfur clusters (e.g., Fe₂S₂ and Fe₄S₂O₂iron-sulfur-oxygen cluster), and combinations thereof. The anion for anyof these and other metal cation cofactors can be any inorganic ororganic anion, such as a halide, carbonate, phosphate, pyrophosphate,tripolyphosphate, sulfate, sulfide, or a carboxylate (nicotinic acid,isonicotinic acid, acetate, etc.), or a bidentate, tridentate,tetradentate, or other chelating or coordination agent, such as ascorbicacid, citric acid, dimercaprol, gluconic acid, nicotinamide, oxalicacid, 1,10-phenanthroline, picolinic acid, 2-(2′-pyridyl)imidazole,2-(2′-pyridyl)benzimidazole, ethylenediamine, ethylenediaminetetraaceticacid (EDTA), acetylacetonate, and combinations thereof. For oraladministration and GI tract bioavailability, it is more common to use anorganic anion (e.g., acetate, nicotinate, etc.) or a bidentate,tridentate, tetradentate, or other complexed metal cation (e.g.,gluconate, citrate, picolinate, etc.) for a cofactor rather than aninorganic anion (e.g., chloride, sulfate, etc.) to provide the metalcation active portion of the cofactor. In some instances, both thecation and the anion can be active physiological agents, (e.g.,nicotinate salts, since nicotinic acid is niacin, or vitamin B3).Further, in certain complexes, one or more coordination compounds andinorganic anions might associate with a single metal cation, (e.g.,bis-phenanthroline Cr(III) complexes can include two chlorine atomsbonded to the chromium, and Cl⁻ as a counterion to the 1+ chargedcomplex). In specific embodiments, cofactors for use in the compositionsof the present disclosure include calcium acetate, calcium ascorbate,calcium citrate, calcium gluconate, calcium nicotinate, calciumpicolinate, chromium acetate, chromium ascorbate, chromium citrate,chromium gluconate, chromium nicotinate, chromium picolinate, copperacetate, copper ascorbate, copper citrate, copper gluconate, coppernicotinate, copper picolinate, magnesium acetate, magnesium ascorbate,magnesium citrate, magnesium gluconate, magnesium nicotinate, magnesiumpicolinate, manganese acetate, manganese ascorbate, manganese citrate,manganese gluconate, manganese nicotinate, manganese picolinate,potassium acetate, potassium ascorbate, potassium citrate, potassiumgluconate, potassium nicotinate, potassium picolinate, selenium acetate,selenium ascorbate, selenium citrate, selenium gluconate, seleniumnicotinate, selenium picolinate, zinc acetate, zinc ascorbate, zinccitrate, zinc gluconate, zinc nicotinate, zinc picolinate, and mixturesthereof.

For use herein, organic cofactors include, but are not limited to,vitamins A, C, B1, B2, B3, B6, B12, H and K, thiamine pyrophosphate,NADH, NAD+, NADP+, FAD, FADH, pyridoxal phosphate, methylcobalamine,cobalamine, biotin, coenzymes A, B, M and Q10 (ubiquinone), folic acid,tetrahydrofolic acid, menaquinone, ascorbic acid, flavin mononucleotide,coenzyme F420, adenosine 5′-monophosphate, ADP, ATP, cytidinetriphosphate, glutathione, lipoamide, β-carotene,(6R)-5,10-methylenetetrahydrofolate, (6R)-5,10-methylenetetrahydrofolicacid, (6S)-5,6,7,8-tetrahydrofolate, (6S)-5,6,7,8-tetrahydrofolic acid,(R)-lipoate, (R)-lipoic acid, 1,4 benzoquinone, 3′-hydroxyechinenone5,6,7,8-tetrahydropteridine, 5-hydroxy-benzimidazolylcob (I)amide,5-hydroxy-benzimidazolyl-cob(I)amide,7-dimethyl-8-(1-D-ribityl)lumazine,6,7-dimethyl-8-(1-D-ribityl)lumazine, 6-decylubiquinone, 6-hydroxy-FAD,myo-inositol hexakisphosphate, S-adenosyl-L-homocysteine,S-adenosyl-L-methionine zwitterion, S-adenosyl-L-methionine zwitterion,L-ascorbate, L-ascorbic acid, ammonium cation (NH₄ ⁺), bacillithiol,biotinate, bis(molybdopterin)tungsten, chlorophyll a, chlorophyll b,cobamamide, corrin, corrinoid, decylplastoquinone,dehydro-D-arabinono-1,4-lactone, dihydrogen vanadate, dihydrolipoamide,dipyrromethene, dipyrromethene, divinyl chlorophyll a, divinylchlorophyll b, echinenone, Fe-coproporphyrin III, ferriheme a, ferrohemeb, ferroheme cmethanofuran, molybdopterin, various nucleotide sugars,3′-phosphoadenosine-5′-phosphosulfate, quinone, pyrroloquinolinequinone, tetrahydrobiopterin, tetrahydromethylbioterin, prodrugsthereof, pharmaceutically acceptable salts thereof, and combinationsthereof.

As used herein, the term “prodrug” refers to an AAI that is prepared inan inactive form that is converted to an active form within the body orcells thereof by the action of endogenous enzymes or other chemicalsand/or conditions. In various embodiments, a prodrug-AAI is compoundedinto a loose powder composition and loaded into capsules for oraladministration, whereby the prodrug-AAI is converted to the active AAIin the GI tract of the individual.

As used herein, the term “controlled drug release agent” (or moresimply, the acronym “CDRA”), refers to an organic substance capable ofagglomerating around an AAI so as to slow down the bioavailability ofthe AAI in the GI tract. In various embodiments, an AAI may beintimately mixed with a CDRA in a powder composition for capsuledelivery. When the capsule dissolves in the stomach, the CDRA swellswith water, physically trapping the AAI (and other active ingredients)until the GI tract, e.g., catalyzed by acidity and temperature in thegut, can break down the CDRA. In various embodiments, CDRAs for useherein comprise certain particle sizes, and in some instances,nanoparticles. In various embodiments, CDRAs for use herein comprisenatural, semisynthetic and synthetic hydrophilic polymers capable ofgelling and/or swelling. In various embodiments, CDRAs for use hereincomprise hydrogel materials, also known as polymer hydrogels or PHGs.CDRAs for biological applications, such as herein, are generallypolysaccharides or polypeptides. Combinations of hydrogels may be usedto create “core-shell” composite hydrogels. Distinction is made betweena CDRA for use to slow down active drug release and a disintegrant foruse in speeding up drug release, even though in a formal sense, speedingup drug active delivery is still a form of “controlling” drug release.Attempt is made herein to categorize disintegrants with “excipients” andto keep CDRAs in a separate category of ingredients.

CDRAs for use herein include, but are not limited to, agar, agarose,albumin, alginate, casein, chitin, chondroitin, dextrin, fibroin,fucoidans, galactans, gellan, guar, scleroglucan, pullulan, xyloglucan,pectin, xanthan, psyllium, silica gel, fumed silica, magnesium aluminumsilicates, clay, bentonite, hectorite, mesoporous silica, cellulose,cellulose acetate, hyaluronan, various elastin-like polypeptides,O-cyclodextrin, collagen, gelatin, chitosan, carrageenan, polylacticacid, polyglycolic acid, poly(lactic-glycolic acid) (PLGA),poly(2-hydroxyethyl methacrylate), poly(2-hydroxypropyl methacrylate),poly(acrylic acid), carboxymethyl cellulose, carboxyethyl cellulose,hydroxyethyl cellulose, hydrophobically-modified hydroxyethyl cellulose,hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methylcellulose, ethyl cellulose, microcrystalline cellulose, nitrocellulose,polyvinyl alcohol, polyvinylpyrrolidone, polyvinylmethacrylate,carboxyvinyl polymers, polyvinylacetate, polyvinyl co-polymers, variousstarches, modified starches, and combinations thereof. See, S. M. FijulKabir, et al., “Cellulose-based hydrogel materials: chemistry,properties and their prospective applications,”Prog. Biomater., 7,153-174 (2018).

As used herein, the term “immediate release” refers to a pharmaceuticaldosage form designed to fall apart, dissolve, or otherwise disintegrateas quickly as possible. Typically, a dosage form for immediate releasewill be an oral dosage form, such as a tablet for sublingual drugadministration or a capsule for swallowing with subsequent GI drugdelivery. Capsule dosage forms may be designed for immediate drugrelease by changes to either the capsule shell, or the powder fillcomposition, or both. For example, hard capsule shells may belaser-drilled with holes that allow entry of water in the gut. In otherexamples, one or more disintegrating agents (called “disintegrants”) maybe added into the powder fill composition of a capsule, or into thecapsule shell itself. In various embodiments, immediate release may alsobe coupled with increased GI absorption, and in those instances anintestinal permeation enhancer may be included in an immediate releasecomposition so that there is not only rapid dissolution of the capsule,there is also rapid intestinal absorption. In various embodiments, astandard gel cap or powder filled hard gelatin capsule may provideimmediate release in the gut simply in response to physiologicalconditions of heat and acid in the stomach, sufficiently capable ofdissolving a gelatin shell in due course. Immediate release tends to bethe opposite of controlled release or sustained release.

As used herein, the term “nutritive” refers to any substance providingcaloric or other nutritional value to an individual, including anysubstances from the classic food groups of protein, carbohydrate, andfat. A nutritive for purposes herein may also include nutritive fiber,but a distinction will be made between nutritive fiber and fibrousmaterials that swell into hydrogels for controlled drug releasepurposes, such as cellulosic materials. In other words, a cellulosic inan appetite suppressant composition herein is likely present in thecomposition for sustained AAI release purposes rather than for supplyingdigestive fiber. Another example is psyllium, a well-known digestivefiber, but a material that also acts as a CRDA because of its ability toswell in the gut and occlude other materials. In various embodiments, anutritive may comprise a nutritive filler. Said another way, a nutritivesuch as a protein powder may be used in “quantity sufficient” (q.s.) tofill in the remainder of a composition totally 100 wt. %.

As used herein, the term “protein source” refers to an organic substanceor mixture that provides a moderate to a high level of protein, shorterchain peptides, and/or amino acids (e.g., at least about 60 wt. %peptide materials) based on the total weight of the protein material. Invarious embodiments, a protein source may be similar if not identical tosubstances used in protein shakes in the health and fitness industry,and may be animal or plant derived, including aquatic plant. In variousembodiments, a protein source for use herein may be hydrolyzed so thatit can be intestinally absorbed more easily than the parent proteinprior to hydrolysis. Protein sources for use herein include, but are notlimited to, whey, casein, lectin, collagen, egg protein, pea protein,hemp protein, brown rice protein, alfalfa, chia, flax, artichoke,quinoa, a Spirulina algal species, a Chlorella algal species, aSchizochytrium algal species, a Laminaria algal species, an Ulva algalspecies, an Arthrospira algal species, a Porphyridium algal species, aHaematococcus algal species, and combinations thereof. For any of theplant and animal sources of protein, the raw animal or plant material orisolated protein may be left natural or hydrolyzed, and then dried intoa powder. For the algal species, the protein source may comprise thealgal biomass itself (e.g., plant matter simply squeezed out, dried orspray dried, and powdered) or the protein source may be isolated and/orhydrolyzed proteins extracted from the algal sources. See, S. Bleakley,et al., “Algal Proteins: Extraction, Application, and ChallengesConcerning Production,” Foods, 6(5), 33 (2017).

As used herein, the term “filler” refers to non-nutritive materials thatmay be added in quantity sufficient to complete a formula to “100%”total. In various embodiments, appetite suppressant compositionscomprise a number of pharmacologically active substances, such as AAIs,nutritive substances, CRDAs, and cofactors, with the remaindercomprising inert filler. In other embodiments, compositions hereincomprise sufficient nutritive substances, like protein sources, suchthat inert fillers for weight and bulk are not needed. Fillers increaseweight, but typically do not contribute to any pharmacological effect.Pharmaceutically acceptable inert fillers are known to thepharmaceutical arts, and include such substances as monosaccharides anddisaccharides, (mannitol, lactose, dextrose) carbonates (calciumcarbonate), phosphates, (calcium phosphate), and sulfates (calciumsulfate). For an exhaustive listing of pharmaceutically acceptablefillers, see “Handbook of Pharmaceutical Excipients, 6^(th) Edition, R.C Rowe, et al., editors, Pharmaceutical Press, London, 2009.

As used herein, the term “excipient” refers to additional functionalingredients in an appetite suppressant composition, and thus distinctfrom inert filler. Excipient refers to those ingredients that althoughfunctional, play a minor role in the composition. These ingredientstypically include disintegrants, colors, flavorants, sweenteners, andpreservatives.

As used herein, the term “composition” takes on the ordinary meaning informulation chemistry as a combination of ingredients. In variousembodiments, a composition is designed to adopt a particular physicalform, or at least be amenable to physical change into a desired physicalform, which may be the dosage form for a particular treatment regimen.Typically, a composition is made homogeneous by mixing or blending,although not all liquid compositions are colorless and transparent andnot all powder compositions are white and perfectly granular.Compositions comprising an emulsion, dispersion or suspension may behomogeneous because the droplets or particles are evenly spread in acarrier. So, for example, a composition herein may be in the form of athin liquid (having a viscosity at or near that of water), a viscousliquid (having a liquid of viscosity greater than water), a paste, acream, a jelly, a gel, or a powder. Ingredients for a composition hereinare generally shown “as added,” meaning there is a possibility for oneor more chemical reactions between ingredients once the ingredients aremixed together, such as into a common carrier. One skilled in the art offormulation chemistry can recognize whether ingredients might react in amixture. These reactions can include neutralization (e.g., between acidand alkali ingredients), mixed micelle formation (mixed surfactants inliquid systems) or other encapsulation phenomena, hydrolysis, and soforth. In various embodiments, a composition herein comprises a blendedpowder that can be packed into capsules for oral administration. In someinstances, a composition may take into consideration an outer encasingwhen that material is also included in the administration of thecomposition to an individual. For example, a gelatin capsule may beincluded in the listing of ingredients for a composition, or perhapsjust the ingredients of the contents of the capsule may be listed. Invarious embodiments, ingredients in a composition are listed in “weightpercent,” (i.e., “wt. %”), based on the total weight of the composition.For example, 100 milligrams of a composition comprising 40 mg A and 60mg B may be recited as “40 wt. % A and 60 wt. % B, based on the totalweight of the composition,” which necessarily totals to “100 wt. %.” Theactual weight amounts, (e.g., milligrams or grams) generally refers toamounts added for a particular batch size, (e.g., a batch size of powderusable to fill 100 capsules).

As used herein, the term “dosage form” takes on its ordinary meaning inthe pharmaceutical arts as the physical form of a composition designedfor a particular administration route. For example, dosage formsinclude, but are not limited to, injectables, infusible liquids, nasalsprays, nasal gels, topicals such as transdermal creams, ointments andpatches, loose powders, tablets, sublingual tabs, capsules, lozenges,syrups, vapors, and so forth. In various embodiments, compositions ofinterest herein comprise powders, and the dosage form comprises acapsule comprising the powdered composition encased or “encapsulated” inthe capsule or a table comprising the powdered composition compressedinto a shape for oral swallowing or sublingual dissolution.

As used herein, the term “capsule” generally refers to a one or twopiece enclosure for a loose powder, which can be swallowed for oraladministration of the powder contents of the capsule, or a soft-shellfor a liquid composition, otherwise known as a “gel cap”). In general,“soft” capsules for liquids are one piece, whereas “hard” capsules forpowders are two piece. In some instances, the capsule is said to“encapsulate” the powder contained therein, which can be confusingbecause the term “encapsulation” is often used, perhaps more correctlyused to describe a microscale or nanoscale phenomenon rather thandescribing something macroscopic like a drug dosage form. In variousembodiments, capsules for use herein are hard, stable two piece shells,or enclosures, capable of stably holding a powder fill, and capable ofdisintegrating in the gastrointestinal track of an individual. Capsulesfor use herein may comprise any combination of animal gelatin, plantpolysaccharides (carrageenan, etc.), or starch or derivatives thereof.In some instances, capsules may further comprise plasticizers, colors,preservatives, disintegrants, lubricants, and various surface treatmentssuch as laser perforations. In various embodiments, a capsule may betransparent so that the contents are visible, or entirely opaque toobscure the contents. In various embodiments, the rate of delivery of anAAI from a two piece hard capsule having a powder fill may be controlledby any combination of ingredients in the powder fill and ingredients ordesign configurations of the capsule itself. For example, a capsuleintended for immediate release of an active drug may comprise amicronized powder fill in combination with a laser perforated capsulehaving disintegrants incorporated in the capsule material. On the otherhand, a capsule intended for slow or controlled release may have apowder fill configured with a CDRA, like a cellulosic, to coagulate inthe gut, slowing active bioavailability, in combination with a slowerdissolving capsule shell, such as one comprising a plasticizer. Invarious embodiments, an AAI or other bioactive substance may be embeddedin the capsule material.

Two piece hard capsules for use herein can be characterized by a sizescale that includes size 5, 4, 3, 2, 1, 0, 0E, 00, 000, 13, 12, 12e1,11, 10, 7 and Su07, (in increasing order of physical dimensions andinternal volume when assembled). Typically, only the capsule sizes from5 (11.1 mm×4.91 mm, 0.13 mL volume) up through about 000 (26.14 mm×9.91mm, 1.36 mL) would be practical for human oral consumption, anddigestive tract (enteral) route of administration.

As used herein, the term “subject” or the phrase “a subject in needthereof” refers to any human or non-human animal requiring or desirousof a pharmacological change. For example, a subject in need thereof maybe a human patient clinically diagnosed with obesity, an eatingdisorder, or health issues relating to poor BMI, fat along thewaistline, diet in general, or lack of exercise. In various embodiments,the subject in need thereof is a person desirous of a reduced appetitesuch that they can lose weight and/or improve health. Most importantly,a subject in need thereof can be any human in good health, but desirousof maintaining good health. In other words, the subject in need thereofmay be desirous of a prophylactic regimen, like taking daily vitamins.The subject in need thereof may have the outward appearance of a personof average weight for their age, height and gender, but desirous ofmaintaining that weight, and thus desirous of curbing appetite ingeneral.

As used herein, the term “treatment” of a subject (e.g., a human) is anytype of intervention used in an attempt to alter the natural course ofthe subject. Treatment includes, but is not limited to, administrationof an appetite suppressant composition in accordance with the presentdisclosure, and may be performed either prophylactically or subsequentto the initiation of a pathologic event or diagnosis of a physicalissue, such as obesity. Also included are “prophylactic” treatments,which can be directed to reducing the rate of progression of obesity orcondition being treated, delaying the onset of weight or condition, orreducing the severity of its onset. “Treatment” or “prophylaxis” doesnot necessarily indicate complete eradication, cure, or prevention of adisease or condition, or associated symptoms thereof. Treatment may alsobe entirely for cosmetic reasons, such as where an individual has notreceived any diagnosis of having a weight issue or a need for weightloss, but for whom obtaining or maintaining a slim figure is desirousfor some reason, such as to succeed in a particular profession.

As used herein, the term “therapeutically effective amount” refers to aminimum dosage of a composition in accordance with the presentdisclosure that provides a desired effect. Therefore, a therapeuticallyeffective amount varies by subject, dosage form, concentration of one ormore AAIs in the composition, and the ultimate results desired. Forexample, a therapeutically effective amount of a capsule disclosedherein to treat an overweight individual might be on the order of three(3) 150 mg capsules per day. In other examples, a therapeuticallyeffective amount of a capsule disclosed herein to treat a morbidly obeseindividual might be on the order of six (6) 150 mg capsules per day.

As used herein, the term “prophylactically effective amount” refers to aminimum dosage of an appetite suppressant composition in accordance withthe present disclosure that provides maintenance of a desired level ofhealth. Therefore, a prophylactically effective amount varies bysubject, (particularly age, gender, height, weight, and current healthhabits and any ongoing health issues), dosage form, concentration of oneor more AAIs in a composition, and the results desired. For example, aprophylactically effective amount of a capsule composition disclosedherein to promote general health in a male of fairly average weight whoexercises moderately may be one (1) 150 mg capsule per day, such asbefore dinner or when that individual fears overeating.

As used herein, the term “modulate” includes to “increase” or “decrease”one or more quantifiable parameters, optionally by a defined and/orstatistically significant amount. By “increase” or “increasing,”“enhance” or “enhancing,” or “stimulate” or “stimulating,” refersgenerally to the ability of one or more appetite suppressantcompositions in accordance with the present disclosure to produce orcause a greater physiological response (i.e., downstream effects) in acell or in a subject relative to the response caused by either noappetite suppressant composition or a control compound. Relevantphysiological or cellular responses (in vivo or in vitro) uponadministration of appetite suppressant compositions will be apparent topersons skilled in the art. An “increased” or “enhanced” amount istypically a “statistically significant” amount, and may include anincrease that is 1.1, 1.2, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40,50 or more times (e.g., 500, 1000 times), including all integers anddecimal points in between and above 1 (e.g., 1.5, 1.6, 1.7. 1.8), theamount produced by no appetite suppressant composition (the absence of abioactive agent) or a control compound. The term “reduce” or “inhibit”may relate generally to the ability of one or more appetite suppressantcompositions to “decrease” a relevant physiological or cellularresponse, such as a symptom of a disease like obesity or a conditionlike excessive weight described herein, as measured according to routinetechniques in the diagnostic art. Relevant physiological or cellularresponses (in vivo or in vitro) will be apparent to persons skilled inthe art, and may include reductions in the symptoms or pathology of adisease such as obesity and related issues like inflammation or pain. A“decrease” in a response may be “statistically significant” as comparedto the response produced by no appetite suppressant composition or acontrol composition, and may include a 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%,9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%,35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%decrease, including all integers in between.

As used herein, the term “naturally occurring” refers to an AAI obtainedin its active form from nature. In various embodiments, it is possiblethat an AAI is not identifiable or characterizable in a natural form.For example, an AAI for use herein may be a dried and powdered plantleaf, containing hundreds of structurally complex organic substances,but which acts as an AAI even though there is no way to conclusively saywhat substance or substances in the complex mixture is providing theobserved physiological effect, i.e., appetite suppression. In otherwords, the true active or actives in a natural material, like a groundleaf, may never be known, but for simplicity, the natural material maybe referred to as an AAI because of the effect it can elicit.

As used herein, the term “semisynthetic” refers to an AAI obtained byone or more reactions in synthetic organic chemistry, beginning with anaturally occurring substance. In other words, a naturally occurringsubstance may need to undergo one or more synthetic steps in alaboratory or chemical process plant to be ultimately useful as an AAIfor a composition herein.

As used herein, the term “synthetic” refers to an AAI that is madeentirely by organic synthesis, such as through a linear or convergentstrategy, possibly involving asymmetric synthesis as needed to obtain aspecific enantiomer of an AAI, such as directing formation of a chiralcenter using a chiral reagent.

As used herein, the term “approximately” in reference to amounts refersto plus or minus 5% of the value given, such as wt. %. The term “about,”a in reference to amounts refers to plus or minus 10% of the valuegiven, such as wt. %.

GENERAL EMBODIMENTS

In various embodiments, an appetite suppressant composition inaccordance with the present disclosure comprises: at least one AAI; andany one or combination of a nutritive substance, a CDRA, a cofactor, anexcipient, and/or a filler. In various embodiments, the AAI is selectedfrom the group consisting of phentermine, diethylpropion,phendimetrazine, bupropion, naltrexone, prodrugs thereof,pharmaceutically acceptable salts thereof, and combinations thereof. Invarious embodiments, the nutritive substance comprises a protein source.In various embodiments, the CDRA comprises a cellulosic. In variousembodiments, the appetite suppressant composition is in the physicalform of a loose powder for filling capsules, and wherein the dosage formto administer the composition comprises an extended release capsule. Invarious embodiments, the CDRA component is absent in the loose powdercomposition, and the dosage form to administer the composition comprisesan immediate release capsule.

(I) In various embodiments, an appetite suppressant composition inaccordance with the present disclosure comprises: at least one AAI; anutritive substance; a CDRA; a cofactor; and optional excipients. Invarious embodiments, the AAI is selected from the group consisting ofphentermine, diethylpropion, phendimetrazine, bupropion, naltrexone,prodrugs thereof, pharmaceutically acceptable salts thereof, andcombinations thereof. In various embodiments, the nutritive substancecomprises a protein source. In various embodiments, the CDRA comprises acellulosic. In various embodiments, the appetite suppressant compositionis in the physical form of a loose powder for filling capsules, andwherein the dosage form to administer the composition comprises anextended release capsule.

(II) In various embodiments, an appetite suppressant composition inaccordance with the present disclosure comprises: at least one AAI; aCDRA; and optional excipients. In various embodiments, the AAI isselected from the group consisting of v In various embodiments, the CDRAcomprises a cellulosic. In various embodiments, the appetite suppressantcomposition is in the physical form of a loose powder for fillingcapsules, and wherein the dosage form to administer the compositioncomprises an extended release capsule.

(III) In various embodiments, an appetite suppressant composition inaccordance with the present disclosure comprises: at least one AAI; anutritive substance; a cofactor; and optional excipients. In variousembodiments, the AAI is selected from the group consisting ofphentermine, diethylpropion, phendimetrazine, bupropion, naltrexone, andcombinations thereof. In various embodiments, the appetite suppressantcomposition is in the physical form of a loose powder for fillingcapsules, and wherein the dosage form to administer the compositioncomprises an immediate release capsule.

In these general embodiments of appetite suppressant compositions, theat least one AAI is present (at a combined weight if more than one) fromabout 0.1 wt. % to about 10.0 wt. %, based on the total weight of thecomposition, and depending on the actual AAI chemical species used andthe desired strength of the AAI(s) in the finished dosage form. Invarious embodiments, any AAI may be in the form of a pharmaceuticallyacceptable salt, such as the hydrochloride salt, or tartrate salt, orother salt to provide a more water soluble form.

In general embodiments of appetite suppressant compositions comprising aprotein source as the nutritive substance, the protein source may beselected from the group consisting of a dried Spirulina algal speciesbiomass powder having >about 60 wt. % protein (e.g., S. platensis, S.maxima), a dried Chlorella algal species biomass powder having >about 60wt. % protein (e.g., C. pyrenoidosa, C. vulgaris), (available fromNanjing NutriHerb BioTech Co., LTD, Nanjing, China), a hydrolyzedpowdered animal collagen (e.g., bovine or fish), a gelatin powder (e.g.,bovine or porcine collagen that has been partially hydrolyzed), eggalbumin powder, calcium caseinate powder, powdered milk proteinconcentrate (many of the above-mentioned animal derived protein rawmaterial powders are available from Heathy Solutions, LLC, ScottsdaleAriz., USA), whey protein isolate powder (from Antler Farms®, HornbySouth, Christchurch, New Zealand), or a dried legume, grain, vegetable,nut or seed protein isolate or hydrosylate powder (from brown rice,lentils, yellow pea, or hemp seeds, particularly yellow pea proteinisolate), available, e.g., from AXIOM Foods, Los Angeles, Calif., USA.See, J. Y. Nehete, “Natural proteins: Sources, isolation,characterization and applications,”Pharmacogn. Rev., 7(14) 107-116(2013).

Table 1 sets forth these three general embodiments (I, II, III) inaccordance with the present disclosure. The compositions are in thephysical form of a loose powder, which can be loaded into capsules toprovide dosage forms for oral administration. General embodiments I andII encompass the compositions for use in a controlled (extended) releasedosage form, whereas general embodiment III encompasses the compositionsfor use in an immediate release dosage form. In any of the specificcompositions under I, II, and III, the loose fill composition may beloaded into two-piece hard shell capsules. The capsule shell may bemodified as necessary to be more appropriate for controlled releaseversus immediate release.

TABLE 1 General Appetite Suppressant Compositions CompositionsIngredient (wt. %) I II III Anorectic Active Ingredient(s) (AAI) 4 to 2540 to 65 5 to 20 Controlled Drug Release Agent (CDRA) 40 to 50 35 to 60-0- Nutritive Substance (e.g., a protein source) 10 to 50 -0- 50 to 85Cofactor 0.01 to 0.1 -0- 0.01 to 0.1 Excipients (color, flavor, etc.) 0to 40 0 to 40 0 to 40 Total 100.00 wt. % 100.00 wt. % 100.00 wt. %Physical Appearance Loose powder Loose powder Loose powder Use ExtendedExtended Immediate Release Release Release

In various embodiments, any combination of the at least one nutritivesubstance and the at least one CDRA may be used to bulk the composition“quantity sufficient” to 100% total. In other words, the AAI and thecofactor are likely to be the most important in a dosage regimen,whereas the CDRA, like a cellulosic substance, and the nutritivesubstance, like a protein powder, can vary as necessary to make up theremainder of a capsule fill.

In various embodiments, the AAI is selected from the group consisting ofphentermine, diethylpropion, phendimetrazine, bupropion, naltrexone, andcombinations thereof. In various embodiments, the AAI consists ofphentermine used on its own. In various embodiments, the AAI isphentermine-HCl. In various embodiments, consists of phendimetrazineused on its own. In various embodiments, the AAI is phendimetrazinetartrate. In various embodiments, the AAI is diethylpropion used on itsown. In various embodiments, the AAI is diethylpropion HCl with 1%tartaric acid. In various embodiments, the AAI is a combination ofnaltrexone and bupropion. In various embodiments, the AAI is a mixtureof naltrexone-HCl and bupropion-HCl.

In various embodiments, the appetite suppressant composition contain noinert filler, although recognizing a cellulosic CDRA is non-nutritive,and thus acts as a filler as discussed above. In other words, in certainvariations, the only non-nutritive substance in an appetite suppressantcomposition in accordance with the present disclosure is the CDRA, suchas if it is cellulosic and hence not digestible.

In various embodiments, an appetite suppressant composition inaccordance with the present disclosure comprises any combination ofoptional excipients. In various embodiments, an appetite suppressantcomposition contains no excipients. In some instances, there is no tasteto mask in a swallowed capsule, and perhaps no need for colorants,sweeteners or preservatives. Depending on the AAI, and whether a filledcapsule is designed for extended release or immediate release, it may benecessary to include a flavorant.

In various embodiments, the optional one or more excipients include anyone or combination of flavorant, sweetener, buffer (or acidic agentand/or alkali agent), colorant, disintegrant, intestinal permeationenhancer, stabilizer, preservative, or other pharmaceutically acceptablesubstance. Any of these materials not specifically mentioned herein maybe found in “Handbook of Pharmaceutical Excipients, 6^(th) Edition, R. CRowe, et al., editors, Pharmaceutical Press, London, 2009, mentionedabove in the context of “fillers.” For liquid excipients, or excipientsthat might be better dispersed if provided in solution, the substancemay be sprayed into a ribbon blender with a spray bar as a powderedcomposition is blending. In this way, a dry blended powder is stillobtained, even though small amounts of liquid ingredients are absorbedin homogeneously.

Suitable flavorants can include, for example, flavors, such as, naturalflavors, artificial flavors, and combinations thereof. Non-limitingexamples of flavor oils include spearmint oil, cinnamon oil, oil ofwintergreen (methyl salicylate), peppermint oil, clove oil, bay oil,anise oil, eucalyptus oil, thyme oil, cedar leaf oil, oil of nutmeg,allspice, oil of sage, mace, oil of bitter almonds, and cassia oil.Suitable flavoring agents also include, for example, artificial, naturaland synthetic fruit flavors such as vanilla, citrus oils (e.g., lemon,orange, lime, and grapefruit), and fruit essences (e.g., apple, pear,peach, grape, strawberry, raspberry, cherry, plum, pineapple, andapricot), and the like, and combinations thereof.

Other flavorants and fragrant aromatics that may be includedindividually or in combination include, but are not limited to,anethole, menthol, menthone, menthyl acetate, eucalyptol, borneol,borneol acetate, camphor, 1,8-cineole, cinnamaldehyde, benzaldehyde,citral, thuj one, eugenol, limonene, geraniol, citronellol, citronellal,pinene, linalool, thymol, carvone, caryophyllene, linalyl acetate,methyl salicylate, and mixtures thereof. Also, substances that providescent and flavor include, but are not limited to,3,3,5-trimethylcyclohexanol, methoxycyclohexanol, benzyl alcohol, anisealcohol, cinnamyl alcohol, β-phenyl ethyl alcohol (2-phenylethanol),cis-3-hexenol, musk xylol, isoeugenol, methyl eugenol, α-amylcinnamicaldehyde, anisaldehyde, n-butyl aldehyde, cumin aldehyde, cyclamenaldehyde, decanal, isobutyl aldehyde, hexyl aldehyde, heptyl aldehyde,n-nonyl aldehyde, nonadienol, hydroxycitronellal, benzaldehyde, methylnonyl acetaldehyde, dodecanol, α-hexylcinnamic aldehyde, undecenal,heliotropin, vanillin, ethyl vanillin, methyl amyl ketone, methylβ-naphthyl ketone, methyl nonyl ketone, musk ketone, diacetyl, acetylpropionyl, acetyl butyryl, acetophenone, p-methyl acetophenone, ionone,methyl ionone, amyl butyrolactone, diphenyl oxide, methyl phenylglycidate, γ-nonyl lactone, coumarin, cineole, ethyl methyl phenylglycidate, methyl formate, isopropyl formate, linalyl formate, ethylacetate, octyl acetate, methyl acetate, benzyl acetate, butylpropionate, isoamyl acetate, isopropyl isobutyrate, geranyl isovalerate,allyl capronate, butyl heptylate, octyl caprylate octyl, methylheptynecarboxylate, methine octynecarboxylate, isoacyl caprylate, methyllaurate, ethyl myristate, methyl myristate, ethyl benzoate, benzylbenzoate, methylcarbinylphenyl acetate, isobutyl phenylacetate, methylcinnamate, cinnamyl cinnamate, ethyl anisate, methyl anthranilate, ethylpyruvate, ethyl α-butyl butylate, benzyl propionate, butyl acetate,butyl butyrate, p-tert-butylcyclohexyl acetate, cedryl acetate,citronellyl acetate, citronellyl formate, p-cresyl acetate, ethylbutyrate, ethyl caproate, ethyl cinnamate, ethyl phenylacetate, ethylenebrassylate, geranyl acetate, geranyl formate, isoamyl salicylate,isoamyl isovalerate, isobornyl acetate, linalyl acetate, methylanthranilate, methyl dihydrojasmonate, β-phenylethyl acetate,trichloromethylphenyl carbinyl acetate, terpinyl acetate, vetiverylacetate, and mixtures thereof.

Suitable sweeteners include nutritive carbohydrates such as sucrose,glucose, fructose, glucose, trehalose, galactose, mannitol, sorbitol,xylitol and artificial sweeteners such as saccharin, aspartame,acesulfame K, cyclamates, neotame, sucralose, stevia, and neohesperidindihydrochalcone (NHDC).

Suitable buffers may comprise one or more acidifying agents or alkalineagents as necessary to neutralize various co-ingredients, form salts ofvarious co-ingredients, and/or achieve a particular pH target for thecomposition, such as to adjust the local environment in the GI tract asa dosage form dissolves. For liquid appetite suppressant compositions,it may be desirable to adjust the pH of the liquid composition.Combinations of various acidifying agents and alkaline agents may beused to create buffering systems that stabilize the desired final pH ofthe composition. Buffers may be mixed buffers, meaning that the alkalineagent is not necessarily the conjugate base of the acidifying agent.

Exemplary acidifying agents for use in the present compositions include,but are not limited to, organic acids of any molecular weight andmineral acids (inorganic acids), and mixtures thereof. Organic acids mayinclude mono-carboxylic acids, di-carboxylic acids, or tri-carboxylicacids, and may be saturated or may have any degree of unsaturation. Forexample, organic acids for use in various embodiments of the compositionin accordance to the present disclosure may include, but are not limitedto, formic acid, carbonic acid, acetic acid, lactic acid, oxalic acid,propionic acid, valeric acid, enanthic acid, pelargonic acid, butyricacid, lauric acid, docosahexaenoic acid, eicosapentaenoic acid, pyruvicacid, acetoacetic acid, benzoic acid, salicylic acid, aldaric acid,fumaric acid, glutaconic acid, traumatic acid, muconic acid, malonicacid, malic acid, succinic acid, glutaric acid, adipic acid, pimelicacid, suberic acid, azelaic acid, abietic acid, pimaric acid, sebacicacid, phthalic acid, isophthalic acid, terephthalic acid, maleic acid,citric acid, and combinations thereof.

Exemplary alkaline materials include any organic amines, NH₃, alkalimetal or alkaline earth hydroxide, any conjugate bases of any organicacids (e.g. R—COO⁻), and any of the salts of carbonic acid, phosphoricacid, nitric acid and sulfuric acid, and any mixtures thereof. Forexample, alkaline materials for use in various embodiments of thecomposition in accordance to the present disclosure may include, but arenot limited to, NaOH, KOH, NH₃, sodium acetate, sodium succinate,disodium succinate, monosodium citrate, disodium citrate, trisodiumcitrate, NaH₂PO₄, Na₂HPO₄, Na₃PO₄, KH₂PO₄, K₂HPO₄, K₃PO₄, NaHSO₄,Na₂SO₄, KHSO₄, K₂SO₄, NaHCO₃, Na₂CO₃, KHCO₃, K₂CO₃, NaH₃P₂O₇, Na₂H₂P₂O₇,Na₃HP₂O₇, Na₄P₂O₇, KH₃P₂O₇, K₂H₂P₂O₇, K₃HP₂O₇, K₄P₂O₇, and mixturesthereof. Any of these chemical species may exist as various hydrateswhen purchased as raw materials for use in the present compositions.

Exemplary colorants include the pharmaceutically acceptable colors usedfor capsules and tablet dosage forms, such as the US FDA certifiedcolors, dyes and lakes for use in pharmaceutical capsules, tablets andsyrups. These acceptable colorants include the inorganic pigments suchas titanium dioxide, yellow iron oxide, red iron oxide and black ironoxide, the organic pigments such as D&C Red 36, Red 30 and Red 34, thesolvent soluble colors D&C Yellow 11, Yellow 7, Red 27, Red 21, Red 17,Green 6, and Violet 2, and the water soluble colors D&C Green 8, Yellow10, Yellow 8, Orange 4, Red 22, Red 28, Red 33, Green 5, quinolineyellow, FD&C Yellow 5, Yellow 6, Red 4, Red 40, Red 3, Green 3, Blue 1,Blue 2, and ponceau 4R, carmoisine, amaranth, patent blue V and blackPN, and a number of “organic lakes.”

Suitable disintegrants include, but are not limited to, sodium starchglycolate, croscarmellose sodium, microcrystalline cellulose, andcrospovidone. Some substances known to be disintegrants can act as CDRAsas well, since the swelling of an ingredient can not only break apartother structures but can occlude drug actives. For a review ofdisintegrants that find use in the present compositions, see P. M.Desai, “Review of Disintegrants and the Disintegration Phenomena,”J.Pharm. Sci., 105, 2545-2555 (2016).

Suitable intestinal permeation enhancers include, but are not limited tosurfactants that assist bio-absorption, including, for example, fattyacids and/or esters or salts thereof, bile acids and/or salts thereof.Bile acids/salts and fatty acids and their uses are further described inU.S. Pat. No. 6,287,860, which is incorporated herein in its entirety.In some embodiments, the present disclosure provides combinations ofabsorption enhancers, for example, fatty acids/salts in combination withbile acids/salts. An exemplary combination is the sodium salt of lauricacid, capric acid and ursodeoxycholic acid (UDCA) for promoting improvedintestinal absorption of peptides and other materials. These excipientsmay be used in the present compositions to assist absorption of the AAIand/or the protein source, such as hydrolyzed animal or plant proteins.Further penetration enhancers include, but are not limited to,polyoxyethylene-9-lauryl ether, polyoxyethylene-20-cetyl ether. For areview of absorption enhancers that find use herein, see B. J. Aungst,“Intestinal Permeation Enhancers,”J. Pharm. Sci., 89(4), 429 (2000).

Stabilizers and preservatives are generally more important for liquidcompositions rather than dry powder compositions. Such substances fororal compositions include the parabens, sorbitol, sodium benzoate,benzoic acid, sorbic acid, potassium sorbate, propionic acid, andcombinations thereof. Antioxidants include, but are not limited to,vitamin C, vitamin E, butylated hydroxyanisole (BHA), butylatedhydroxytoluene (BHT), and propylgallate. In some instances, theantioxidant, such as a vitamin, can double as a nutritive substance inthe appetite suppressant composition. For a review see, I. Himoudy,“Preservatives and their role in pharma and clinical research,”International Journal of Pharma Sciences and Scientific Research, 2:4,134-151 (2016).

The appetite suppressant compositions of the present disclosure may alsoinclude surfactants. The use of surfactants in drug products,formulations and in emulsions is well known in the art. Surfactants andtheir uses are further described in U.S. Pat. No. 6,287,860, which isincorporated herein in its entirety.

Exemplary Compositions, Dosage Forms, and Methods of Administration

Table 2 sets forth exemplary appetite suppressant compositions inaccordance with the present disclosure. Each of these compositions areobtained by dry-blending each of the dry ingredients in a V-blender(e.g., MAXIBLEND® lab blender) or other suitable mixer configured formixing dry ingredients. Liquid colorants may be sprayed into the blenderwith a spray nozzle. Each of the exemplary composition in Table 2 appearas loose powders and each were filled into two-piece hard shell capsulesat the fill weights indicated.

TABLE 2 Exemplary Appetite Suppressant Compositions and Dosages:Ingredient Composition (wt. %) 1 2 3 4 5 6 7 8 9 AAI 4.80¹ 7.35¹ 14.42¹13.50¹ 15.37² 9.10³ 25.41³ 42.95⁴ 63.57⁴ CDRA 44.62⁵ 45.50⁵ 44.62⁵40.34⁵ -0- -0- 47.42⁵ 57.01⁶ 36.40⁶ Nutritive⁷ 50.50 47.07 40.88 46.1084.55 54.50 10.16 -0- -0- Cofactor⁸ 0.08 0.08 0.08 0.06 0.08 0.07 0.07-0- -0- Excipients⁹ -0- -0- -0- -0- -0- 36.33 16.94 0.04 0.03 Total 100%100% 100% 100% 100% 100% 100% 100% 100% Capsule Fill 260 mg 255 mg 260mg 347mg 260 mg 275 mg 295mg 256 mg 346 mg

TABLE 2 notes: (1) preferably phentermine-HCl; (2) preferablyphendimetrazine tartrate; (3) preferably diethylpropion-HCl with 1%tartaric acid; (4) preferably a 1:10 ratio of naltrexone-HCl tobupropion-HCl; (5) preferably hydroxypropyl methylcellulose; (6)preferably a 10:1 to about a 3:1 ratio of hydroxypropyl methylcelluloseand microcrystalline cellulose; (7) preferably hydrolyzed collagen; (8)preferably chromium picolinate; and (9) preferably combinations ofpeppermint flavorant and/or colorants. The empty gelatin capsules usedin these examples were size 1 (70 mg empty) and size 0 (90 mg empty).

Besides cellulosic CDRAs, which arguably are fillers in a sense, beingnon-digestive, the appetite suppressant compositions of Table 2 areabsent inert fillers typically used in capsule and other oral dosageforms to provide bulk and weight. Thus, in various embodiments, appetitesuppressant compositions according to the present disclosure comprise noinert filler.

In various embodiments, the AAI is selected from the group consisting ofdiethylpropion, amphetamine, benfluorex, bupropion, butanolide,caffeine, cathine, cetilistat, clobenzorex, D-fenfluramine,racemic-fenfluramine, ephedrine, etilamfetamine, exenatide, FG-7142(diazepine inverse agonist), higenamine, liraglutide, lorcaserin,mazindol, mefenorex, metformin, methamphetamine, naltrexone, nicotine,orlistat, phenmetrazine, phendimetrazine, phentermine,phenylpropanolamine, pramlinatide, pseudoephedrine,pyroglutamyl-histidyl-glycine, rimonabant, semaglutide, sibutramine,topiramate, yohimbine, pro-drugs thereof, pharmaceutically acceptablesalts thereof, and combinations thereof.

In various embodiments, the CDRA, when present for a controlled releasecomposition, is selected from the group consisting of agar, agarose,albumin, alginate, casein, chitin, chondroitin, dextrin, fibroin,fucoidan, galactan, gellan, guar, scleroglucan, pullulan, xyloglucan,pectin, xanthan, psyllium, silica gel, fumed silica, magnesium aluminumsilicate, clay, bentonite, hectorite, mesoporous silica, cellulose,cellulose acetate, hyaluronan, elastin-like polypeptides,β-cyclodextrin, collagen, gelatin, chitosan, carrageenan, polylacticacid, polyglycolic acid, poly(lactic-glycolic acid) (PLGA),poly(2-hydroxyethyl methacrylate), poly(2-hydroxypropyl methacrylate),poly(acrylic acid), carboxymethyl cellulose, carboxyethyl cellulose,hydroxyethyl cellulose, hydrophobically-modified hydroxyethyl cellulose,hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methylcellulose, ethyl cellulose, microcrystalline cellulose, nitrocellulose,polyvinyl alcohol, polyvinylpyrrolidone, polyvinylmethacrylate,carboxyvinyl polymers, polyvinylacetate, polyvinyl co-polymers, starch,modified starches, and combinations thereof.

In various embodiments, the nutritive, when present, is selected fromthe group consisting of a dried Spirulina algal species biomass powder,a dried Chlorella algal species biomass powder, a hydrolyzed powderedbovine or fish collagen, a bovine or porcine gelatin powder, egg albuminpowder, calcium caseinate powder, powdered milk protein concentrate,whey protein isolate powder, yellow pea protein isolate, andcombinations thereof.

In various embodiments, the cofactor, when present, is selected from thegroup consisting of calcium acetate, calcium ascorbate, calcium citrate,calcium gluconate, calcium nicotinate, calcium picolinate, chromiumacetate, chromium ascorbate, chromium citrate, chromium gluconate,chromium nicotinate, chromium picolinate, copper acetate, copperascorbate, copper citrate, copper gluconate, copper nicotinate, copperpicolinate, magnesium acetate, magnesium ascorbate, magnesium citrate,magnesium gluconate, magnesium nicotinate, magnesium picolinate,manganese acetate, manganese ascorbate, manganese citrate, manganesegluconate, manganese nicotinate, manganese picolinate, potassiumacetate, potassium ascorbate, potassium citrate, potassium gluconate,potassium nicotinate, potassium picolinate, selenium acetate, seleniumascorbate, selenium citrate, selenium gluconate, selenium nicotinate,selenium picolinate, zinc acetate, zinc ascorbate, zinc citrate, zincgluconate, zinc nicotinate, zinc picolinate, and mixtures thereof.

In various embodiments, the excipients, when present, are selected fromthe group consisting of flavorants, colorants, and mixtures thereof.

With reference to TABLE 2, compositions 1-7 each benefit from theunusual combination of hydrolyzed bovine collagen and chromiumpicolinate in an extended release oral dosage form. This combinationunexpectedly provides synergistic maintenance of a healthy gut barrier,along with increasing metabolism, stabilizing blood sugar levels,promoting weight loss and body fat, while increasing lean body mass. Thecombination further appears to improve skin elasticity, improve hair andnail appearance, improve muscle mass, improve heart health, relievejoint pain, and prevent bone loss. The hydrolyzed bovine collagen andchromium picolinate in an extended release oral dosage form appears toreduce hunger and cravings, and lower appetite, over extended periods oftime, and may enhance insulin.

The appetite suppressant compositions of the present disclosure may beadministered in a number of ways depending upon whether local orsystemic treatment is desired. Administration may be topical (includingophthalmic and to mucous membranes including vaginal and rectaldelivery), pulmonary, e.g., by inhalation or insufflation of powders oraerosols, including by nebulizer; intratracheal, intranasal, epidermaland transdermal), oral or parenteral. Parenteral administration includesintravenous, intraarterial, subcutaneous, intraperitoneal orintramuscular injection or infusion; or intracranial, e.g., intrathecalor intraventricular, administration. Appetite suppressant compositionsfor topical administration may include transdermal patches, ointments,lotions, creams, gels, drops, suppositories, sprays, liquids andpowders. Conventional pharmaceutically acceptable carriers, aqueous,powder or oily bases, thickeners and the like, may be necessary ordesirable. In various embodiments, appetite suppressant compositionscomprise loose powders that are filled into dissolvable capsules fororal administration and gastrointestinal absorption.

The appetite suppressant compositions of the present disclosure, whichmay conveniently be presented in unit dosage form such as a capsule, maybe prepared according to conventional techniques well known in thepharmaceutical industry. Such techniques include the step of bringinginto association the at least one AAI with the pharmaceuticallyacceptable carrier(s) or excipient(s), which in various embodimentscomprises a nutritive base. In general, the appetite suppressantcompositions are prepared by uniformly and intimately bringing intoassociation the AAI(s) with finely divided solid carriers or both, andthen, if necessary, shaping the product by addition of variousexcipients.

The appetite suppressant compositions of the present disclosure may beformulated into any of many possible dosage forms such as, but notlimited to, tablets, capsules, gel capsules, liquids, liquid syrups,soft gels, suppositories, and enemas. The compositions of the presentdisclosure may also be formulated as suspensions in aqueous, non-aqueousor mixed media. Aqueous suspensions may further contain substances whichincrease the viscosity of the suspension or help to stabilize thesuspension.

One of skill in the art will recognize that compositions are routinelydesigned according to their intended use, i.e., route of administration.

Appetite suppressant compositions for oral administration includepowders or granules, microparticulates, nanoparticulates, capsules, gelcapsules, sachets, tablets or minitablets. Oral formulations are thosein which at least one AAI of the present disclosure is administered inconjunction with one or more CDRAs, surfactants, chelators,bio-absorption promotors such as intestinal permeation enhancers, orother active or nonactive excipients.

Dosage Regimens

In various embodiments of, methods of appetite suppression aredescribed. In general, a method of suppressing appetite in an individualin need thereof comprises orally administering to the individual atherapeutically effective amount of an appetite suppressant compositioncomprising at least one AAI. In various embodiments, the individual inneed thereof has been diagnosed as overweight and obese, as per ICD-10code E66 and subgroups. This diagnosis is discussed in S. B. Gribsholt,et al., “Validity of ICD-10 diagnoses of overweight and obesity inDanish hospitals,” Clin. Epidemiol., 11, 845-854 (2019).

In various embodiments, a method of suppressing appetite in anindividual in need thereof comprising orally administering to theindividual a therapeutically effective amount of an appetite suppressantcomposition comprising: at least one AAI; at least one of a nutritivesubstance, a CDRA, and a cofactor; and optionally an excipient. Invarious embodiments, the AAI is selected from the group consisting ofdiethylpropion, amphetamine, benfluorex, bupropion, butanolide,caffeine, cathine, cetilistat, clobenzorex, D-fenfluramine,racemic-fenfluramine, ephedrine, etilamfetamine, exenatide, FG-7142(diazepine inverse agonist), higenamine, liraglutide, lorcaserin,mazindol, mefenorex, metformin, methamphetamine, naltrexone, nicotine,orlistat, phenmetrazine, phendimetrazine, phentermine,phenylpropanolamine, pramlinatide, pseudoephedrine,pyroglutamyl-histidyl-glycine, rimonabant, semaglutide, sibutramine,topiramate, yohimbine, pro-drugs thereof, pharmaceutically acceptablesalts thereof, and combinations thereof. In various embodiments, the AAIis selected from the group consisting of phentermine, diethylpropion,phendimetrazine, bupropion, naltrexone, prodrugs thereof,pharmaceutically acceptable salts thereof, and combinations thereof.

Appetite suppressant compositions of the present disclosure may bedelivered orally, in granular form including sprayed dried particles, orcomplexed to form micro or nanoparticles, which may be administered as aloose powder that can be mixed into a beverage, or packed into capsulesfor swallowing. In various embodiments, the appetite suppressantcomposition comprise dry blended loose powders, with the dosage formcomprising a capsule comprising the dry blended loose powder containedtherein.

Capsule dosages are in large part based on the AAI(s) present in thepowder composition within the capsule. Generally, the following dosageregimens apply for those individuals in need thereof that receivedICD-10 diagnosis:

Phentermine—dosing up to 75 mg daily, with a time period of up to twicedaily;

Diethylpropion—dosing up to 150 mg daily, with a time period of up tofour times daily;

Phendimetrazine—dosing up to 210 mg daily, with a time period of up tothree times daily; and

Bupropion/Naltrexone—dosing up to 400 mg/40 mg daily, with a time periodof up to twice daily.

For the preferred AAIs in the compositions and capsules outlined inTable 2, the following amounts and dosages are relevant:

Composition 1: each capsule contains 12.5 mg phentermine-HCl. Thus, atherapeutically effective amount of composition 1 comprises from 1 up toabout 6 capsules per day;

Composition 2: each capsule contains 18.8 mg phentermine-HCl. Thus, atherapeutically effective amount of composition 2 comprises from 1 up toabout 4 capsules per day;

Composition 3: each capsule contains 37.5 mg phentermine-HCl. Thus, atherapeutically effective amount of composition 3 comprises from 1 toabout 2 capsules per day;

Composition 4: each capsule contains 46.9 mg phentermine-HCl. Thus, atherapeutically effective amount of composition 4 comprises from 1 toabout 2 capsules per day;

Composition 5: each capsule contains 40 mg phendimetrazine tartrate.Thus, a therapeutically effective amount of composition 5 comprises from1 up to about 5 capsules per day;

Composition 6: each capsule contains 25 mg diethylpropion-HCl. Thus, atherapeutically effective amount of composition 6 comprises from 1 up toabout 6 capsules per day;

Composition 7: each capsule contains 75 mg diethylpropion-HCl. Thus, atherapeutically effective amount of composition 7 comprises from 1 up toabout 2 capsules per day;

Composition 8: each capsule contains 10 mg naltrexone-HCl and 100 mgbupropion-HCl. Thus, a therapeutically effective amount of composition 8comprises from 1 up to about 4 capsules per day; and

Composition 9: each capsule contains 20 mg naltrexone-HCl and 200 mgbupropion-HCl. Thus, a therapeutically effective amount of composition 9comprises from 1 up to about 2 capsules per day.

Appetite suppressant compositions and methods thereof are provided. Inthe detailed description herein, references to “various embodiments”,“one embodiment”, “an embodiment”, “an example embodiment”, etc.,indicate that the embodiment described may include a particular feature,structure, or characteristic, but every embodiment may not necessarilyinclude the particular feature, structure, or characteristic. Moreover,such phrases are not necessarily referring to the same embodiment.Further, when a particular feature, structure, or characteristic isdescribed in connection with an embodiment, it is submitted that it iswithin the knowledge of one skilled in the art to affect such feature,structure, or characteristic in connection with other embodimentswhether or not explicitly described. After reading the description, itwill be apparent to one skilled in the relevant art(s) how to implementthe disclosure in alternative embodiments.

Benefits, other advantages, and solutions to problems have beendescribed herein with regard to specific embodiments. However, thebenefits, advantages, solutions to problems, and any elements that maycause any benefit, advantage, or solution to occur or become morepronounced are not to be construed as critical, required, or essentialfeatures or elements of the disclosure. The scope of the disclosure isaccordingly to be limited by nothing other than the appended claims, inwhich reference to an element in the singular is not intended to mean“one and only one” unless explicitly so stated, but rather “one ormore.” Moreover, where a phrase similar to ‘at least one of A, B, and C’or ‘at least one of A, B, or C’ is used in the claims or specification,it is intended that the phrase be interpreted to mean that A alone maybe present in an embodiment, B alone may be present in an embodiment, Calone may be present in an embodiment, or that any combination of theelements A, B and C may be present in a single embodiment; for example,A and B, A and C, B and C, or A and B and C.

All structural, chemical, and functional equivalents to the elements ofthe above-described various embodiments that are known to those ofordinary skill in the art are expressly incorporated herein by referenceand are intended to be encompassed by the present claims. Moreover, itis not necessary for a composition or method to address each and everyproblem sought to be solved by the present disclosure, for it to beencompassed by the present claims. Furthermore, no element, component,or method step in the present disclosure is intended to be dedicated tothe public regardless of whether the element, component, or method stepis explicitly recited in the claims. No claim element is intended toinvoke 35 U.S.C. 112(f) unless the element is expressly recited usingthe phrase “means for.” As used herein, the terms “comprises,”“comprising,” or any other variation thereof, are intended to cover anon-exclusive inclusion, such that a chemical, chemical composition,process, method, article, or apparatus that comprises a list of elementsdoes not include only those elements but may include other elements notexpressly listed or inherent to such chemical, chemical composition,process, method, article, or apparatus.

1. An appetite suppressant composition comprising: at least oneanorectic active ingredient; at least one of a nutritive substance, acofactor; and optionally, an excipient.
 2. The composition of claim 1,wherein the anorectic active ingredient is selected from the groupconsisting of diethylpropion, amphetamine, benfluorex, bupropion,butanolide, caffeine, cathine, cetilistat, clobenzorex, D-fenfluramine,racemic-fenfluramine, ephedrine, etilamfetamine, exenatide, FG-7142(diazepine inverse agonist), higenamine, liraglutide, lorcaserin,mazindol, mefenorex, metformin, methamphetamine, naltrexone, nicotine,orlistat, phenmetrazine, phendimetrazine, phentermine,phenylpropanolamine, pramlinatide, pseudoephedrine,pyroglutamyl-histidyl-glycine, rimonabant, semaglutide, sibutramine,topiramate, yohimbine, pro-drugs thereof, pharmaceutically acceptablesalts thereof, and mixtures thereof.
 3. The composition of claim 1,wherein the nutritive substance is selected from the group consisting ofa dried Spirulina algal species biomass powder, a dried Chlorella algalspecies biomass powder, a hydrolyzed powdered bovine or fish collagen, abovine or porcine gelatin powder, egg albumin powder, calcium caseinatepowder, powdered milk protein concentrate, whey protein isolate powder,yellow pea protein isolate, and mixtures thereof.
 4. The composition ofclaim 1, wherein the cofactor is selected from the group consisting ofcalcium acetate, calcium ascorbate, calcium citrate, calcium gluconate,calcium nicotinate, calcium picolinate, chromium acetate, chromiumascorbate, chromium citrate, chromium gluconate, chromium nicotinate,chromium picolinate, copper acetate, copper ascorbate, copper citrate,copper gluconate, copper nicotinate, copper picolinate, magnesiumacetate, magnesium ascorbate, magnesium citrate, magnesium gluconate,magnesium nicotinate, magnesium picolinate, manganese acetate, manganeseascorbate, manganese citrate, manganese gluconate, manganese nicotinate,manganese picolinate, potassium acetate, potassium ascorbate, potassiumcitrate, potassium gluconate, potassium nicotinate, potassiumpicolinate, selenium acetate, selenium ascorbate, selenium citrate,selenium gluconate, selenium nicotinate, selenium picolinate, zincacetate, zinc ascorbate, zinc citrate, zinc gluconate, zinc nicotinate,zinc picolinate, and mixtures thereof.
 5. The composition of claim 1,wherein the anorectic active ingredient comprises phendimetrazinetartrate, the nutritive substance comprises hydrolyzed powdered bovineor fish collagen, and the cofactor comprises calcium picolinate,chromium picolinate, copper picolinate, magnesium picolinate, manganesepicolinate, selenium picolinate, or zinc picolinate.
 6. A pharmaceuticaldosage form for oral administration comprising: a capsule; and thecomposition of claim 5 enclosed therein.
 7. The composition of claim 1,wherein the anorectic active ingredient comprises diethylpropion-HClwith 1% tartaric acid, the nutritive substance comprises hydrolyzedpowdered bovine or fish collagen, and the cofactor comprises calciumpicolinate, chromium picolinate, copper picolinate, magnesiumpicolinate, manganese picolinate, selenium picolinate, or zincpicolinate.
 8. A pharmaceutical dosage form for oral administrationcomprising: a capsule; and the composition of claim 7 enclosed therein.9. An appetite suppressant composition consisting essentially of: from12.0 wt. % to 18.0 wt. % phendimetrazine tartrate; from 80.0 wt. % to90.0 wt. % bovine collagen; and from 0.05 wt. % to 0.10 wt. % chromiumpicolinate.
 10. A pharmaceutical dosage form for oral administrationcomprising: a capsule; and the appetite suppressant composition of claim9 enclosed therein.
 11. A method of suppressing appetite in anindividual, the method comprising orally administering to the individualin need thereof a therapeutically effective amount of the appetitesuppressant composition of claim
 9. 12. The method of claim 11, whereinthe therapeutically effective amount comprises orally administering upto 210 mg per day of the phendimetrazine tartrate.
 13. The method ofclaim 11, wherein the individual in need thereof is diagnosed overweightand obese.
 14. An appetite suppressant dosage form consistingessentially of: 250 mg to 300 mg of the composition of claim 9 as aloose powder; and a dissolvable capsule encapsulating said composition.15. An appetite suppressant composition consisting essentially of: from6.0 wt. % to 12.0 wt. % diethylpropion-HCl, said diethylpropion-HClincluding 1% tartaric acid; from 50.0 wt. % to 58.0 wt. % bovinecollagen; and from 0.05 wt. % to 0.10 wt. % chromium picolinate.
 16. Apharmaceutical dosage form for oral administration comprising: acapsule; and the appetite suppressant composition of claim 15 enclosedtherein.
 17. A method of suppressing appetite in an individual, themethod comprising orally administering to the individual in need thereofa therapeutically effective amount of the appetite suppressantcomposition of claim
 15. 18. The method of claim 17, wherein thetherapeutically effective amount comprises orally administering up to150 mg per day of the diethylpropion-HCl.
 19. The method of claim 17,wherein the individual in need thereof is diagnosed overweight andobese.
 20. An appetite suppressant dosage form consisting essentiallyof: 250 mg to 300 mg of the composition of claim 15 as a loose powder;and a dissolvable capsule encapsulating said composition.